Monday, August 8, 2011

Will Gene Patents Impede Whole Genome Sequencing?: Deconstructing the Myth That 20% of the Human Genome Is Patented

I am in the process of finalizing an article entitled “Will Gene Patents Impede Whole Genome Sequencing?: Deconstructing the Myth That 20% of the Human Genome Is Patented,” which I think many readers of this blog will find of interest, particularly in light of the recent decision in the Myriad a gene patent case (AMP v. PTO). I will be presenting my work this Thursday at the Intellectual Property Scholars Conference at Depaul Law school in Chicago, and have posted a working draft on SSRN.

In my article, I point out that there is a widely held perception that 20% of human genes are "patented," and that these patents preclude researchers and clinicians from using, studying or even "looking at" the patented genes without obtaining a license or risk being sued for patent infringement. In recent years the basis for this belief has increasingly become obscured.

For example, in AMP v. PTO Judge Lourie states that it “is estimated that . . . By 2005, [the PTO] had granted 40,000 DNA-related patents covering, in non-native form, twenty percent of the genes in the human genome.” In support of this assertion he cites to a law review article: J. Rogers, Can You Patent Genes? Yes and No, 93 J. Pat. & Trademark Off. Soc’y 19, 40 (2010). If you read the article by Rogers, you see that he cites to other secondary sources for the proposition that 20% of human genes are patented. Ultimately, if you trace the string of references back to their primary source, one arrives at the seminal article by Kyle Jensen & Fiona Murray: Intellectual Property Landscape of the Human Genome, 310 Science 239 (2005).

It is no surprise that Judge Lourie believes that 20% of human genes are “patented” - over the years the figure has been quoted so often in so many venues that it has become something of an urban legend. Oftentimes the statement that 20% of human genes are patented is made without any supporting reference (for example, this occurred in a recent article published in Science entitled: The Human Genome (Patent) Project). Other authors, such as Judge Lourie, cite to various secondary sources that parrot the conventional wisdom. But if you trace back through the citations, invariably you will find that the sole basis for the myth that 20% of human genes are patented is the 2005 Science article by Jensen and Murray.

Believing that 20% of human genes are patented, and that a patented gene is effectively off-limits, many have become concerned that whole genome sequencing will result in the infringement of hundreds or even thousands of patents. This specific point was made by Judge Bryson in his dissent to AMP v. PTO. During oral arguments, he asked Myriad's attorney whether Myriad's isolated DNA sequence claims would be infringed by personal whole genome sequencing, to which the attorney essentially responded "no" (the ACLU attorney later voiced his opinion that the patents would cover genome sequencing).

Later during oral arguments, Judge Bryson expressed his concern that whole genome sequencing could result in infringement of thousands of gene patents. His perception that isolated DNA claims create a thicket of patents that will impede personal whole genome sequencing might have contributed to his view that these claims should be declared patent ineligible.

In fact, a careful reading of the supporting online material for the Jensen and Murray article reveals that their study has been grossly misinterpreted by those who claim the 20% of human genes are patented. In fact, those authors only purported to show that, with respect to 20% of human genes known at the time they conducted their study, either (1) the DNA sequence of the gene, or (2) the amino acid sequence encoded by the gene, was mentioned in a US patent claim. The myth that 20% of human genes are “patented” has taken root because too many have incorrectly inferred that the mere “mention” of a gene in a patent claim precludes all uses of the gene.

To better understand the actual implications of Jensen and Murray’s findings, I analyzed the claims from a random sampling of 533 of the 4270 patents identified in their article as “gene patents.” (Jensen and Murray graciously provided me with the entire data set of patents identified in their study). Significantly, I found that, under any reasonable interpretation, 140 of the 533 patents would not be infringed by any form of genetic testing. In fact, many of these patents only claim proteins, or recombinant cells, or methods for using DNA that have nothing to do with DNA sequencing. The implicit assumption that the “gene patents” identified by Jensen and Murray cover all uses of the gene (or in some cases corresponding protein) mentioned in the patent claims is clearly false.

The remaining 393 patents include claims with respect to which I cannot entirely rule out the possibility that at least some form of genetic testing would be found infringing. These claims fall into two categories - products claims directed to polynucleotides (e.g., DNA molecules), and method claims that might cover at least some forms of genetic testing. The language used in these claims is extremely heterogeneous, and it is impossible to predict with any certainty exactly how broadly a court would interpret their scope if they were ever asserted in litigation, but to varying degrees a majority of these patents would appear not to be infringed by at least some, perhaps all, forms of genetic testing.

Perhaps most significantly, few (if any) of these patents would appear likely to be infringed by next-generation whole genome sequencing technologies, particularly those that do not require DNA amplification.

In short, there is absolutely no basis to infer from the Jensen & Murray article that 20% of human genes are off-limits to the patents, nor that whole genome sequencing, and other multiplex genetic diagnostic testing technologies, would result in the infringement of a large number of human gene patents. To the contrary, it appears that a vast majority of these patents were drafted in a manner that would not encompass whole genome sequencing.

15 comments:

First, I totally agree with you and Myriad's attorney that the composition claims in Myriad's BRCA1/2 portfolio would not be infringed by whole genome sequencing. I'll take it a step further and say that the composition claims in Myriad's BRCA1/2 portfolio would not be infringed by exon amplification/sequencing either. As you know, the way Myriad does its test is by amplifying the coding regions (and parts of the non-coding regions), sequencing the amplicons, and comparing the amplicon sequences to reference sequences. There's no doubt that the full-length cDNA claims are not implicated here. The only question is whether the fragment claims (any 15 nucleotides of the cDNA) are implicated. Forgetting for a moment that the fragment claims are certainly invalid (102/103), even if they are valid, I still don't think they would be infringed. Truth is, the amplicons are not being "isolated" during the amplification and sequencing process.

Thank you for debunking this 'urban legend' and preventing if from further slowing beneficial clinical developments - developments that can only stem from commercialization, and investments which require a strong IP position.

I agree with second "Anonymous" comment regarding BRCA exon amplification/sequencing. Bob Cook-Deegan and I made that exact point in our amicus brief filed in AMP v. PTO. Our brief is availabe on this blog in an earlier post.

About Me

I am a law professor at the University of Missouri-Kansas City School of Law. My primary research interests lie at the intersection of biotechnology and intellectual property. This blog provides analysis and commentary on recent developments relevant to this area of the law.